Dynamic location problems with limited look-ahead

Background Among the most frequently encountered mutations in dilated cardiomyopathy (DCM) are those in the lamin A/C (LMNA) gene. Our goal was to analyze the LMNA gene in patients with DCM and/or conduction disease referred to the cardiogenetics outpatient clinic and to evaluate the prevalence of LMNA mutations and their clinical expression. Methods and Results The LMNA gene was screened in 61 index patients. Eleven mutations (including 6 novel) were identified, mainly in the subgroup of familial DCM with cardiac conduction disease (3/10 index patients) and in patients with DCM and Emery-Dreifuss, Limb-Girdle, or unclassified forms of muscular dystrophy (7/8 index patients). In addition, a mutation was identified in 1 of 4 families with only cardiac conduction disease. We did not identify any large deletions or duplications.Genotype-phenotype relationships revealed a high rate of sudden death and cardiac transplants in carriers of the p.N 195K mutation. Our study confirmed that the p.R225X mutation leads to cardiac conduction disease with late or no development of DCM, underscoring the importance of this mutation in putative familial "lone conduction disease." Nearly one third of LMNA mutation carriers had experienced a thromboembolic event. Conclusions This study highlights the role of LMNA mutations in DCM and related disorders. A severe phenotype in p.N 195K mutation carriers and preferential cardiac conduction disease in p.R225X carriers was encountered. Because of the clinical variability, including the development of associated symptoms in time, LMNA screening should be considered in patients with DCM or familial lone conduction diseas

A randomized controlled trial of eplerenone in asymptomatic phospholamban p.Arg14del carriers

INTRODUCTION Phospholamban (PLN; p.Arg14del) cardiomyopathy is an inherited disease caused by the pathogenic p.Arg14del variant in the PLN gene. Clinically, it is characterized by malignant ventricular arrhythmias and progressive heart failure.1,2 Cardiac fibrotic tissue remodelling occurs early on in PLN p.Arg14del carriers.3,4 Eplerenone was deemed a treatment candidate because of its beneficial effects on ventricular remodelling and antifibrotic properties.5,6 We conducted the multicentre randomized trial ‘intervention in PHOspholamban RElated CArdiomyopathy STudy’ (i-PHORECAST) to assess whether treatment with eplerenone of asymptomatic PLN p.Arg14del carriers attenuates disease onset and progression

A randomized controlled trial of eplerenone in asymptomatic phospholamban p.Arg14del carriers

Phospholamban (PLN; p.Arg14del) cardiomyopathy is an inherited disease caused by the pathogenic p.Arg14del variant in the PLN gene. Clinically, it is characterized by malignant ventricular arrhythmias and progressive heart failure.1,2 Cardiac fibrotic tissue remodelling occurs early on in PLN p.Arg14del carriers.3,4 Eplerenone was deemed a treatment candidate because of its beneficial effects on ventricular remodelling and antifibrotic properties.5,6 We conducted the multicentre randomized trial ‘intervention in PHOspholamban RElated CArdiomyopathy STudy’ (i-PHORECAST) to assess whether treatment with eplerenone of asymptomatic PLN p.Arg14del carriers attenuates disease onset and progression

Catalytic Conversion of Lignocellulosic Biomass:Application of Heterogeneous and Homogeneous Catalysts to Process Biomass into Value-Added Compounds

Dwindling supplies of fossil resources and the negative impact on the environment associated with their combustion is spurring the exploitation of alternative renewable resources for obtaining fuels and chemicals. Lignocellulosic biomass is the most abundant source of renewable carbon. Its conversion into industrial chemicals is hampered by the lack of catalytic systems able to process this feedstock into usable products in an economically viable manner, among other reasons. Yet, significant progress has been made by employing lessons learned from the field of homogeneous and heterogeneous catalysis for the production of essential chemicals in the past. In this chapter, we will discuss the application of state-of-the-art heterogeneous and homogeneous catalyst technology with the potential to process lignocellulose to valuable platform molecules.</p

Early transition metal doped tungstite as an effective catalyst for glucose upgrading to 5-Hydroxymethylfurfural

Glucose valorization to 5-hydroxymethylfurfural (HMF) remains challenging in the transition towards renewable chemistry. Lewis acidic tungstite is a viable, moderately active catalyst for glucose dehydration to HMF. Literature reports a multistep mechanism involving Lewis acid catalyzed isomerization to fructose, which is then dehydrated to HMF by Brønsted acid sites. Doping tungstite with titanium and niobium improves activity by optimizing the ratio between Lewis and Brønsted acid sites. Graphical Abstract: [Figure not available: see fulltext.

Are they really termites? (Revised 1981)

1 online resource (PDF, 2 pages)This archival publication may not reflect current scientific knowledge or recommendations. Current information available from the University of Minnesota Extension: https://www.extension.umn.edu

Catalytic Conversion of Lignocellulosic Biomass:Application of Heterogeneous and Homogeneous Catalysts to Process Biomass into Value-Added Compounds

Dwindling supplies of fossil resources and the negative impact on the environment associated with their combustion is spurring the exploitation of alternative renewable resources for obtaining fuels and chemicals. Lignocellulosic biomass is the most abundant source of renewable carbon. Its conversion into industrial chemicals is hampered by the lack of catalytic systems able to process this feedstock into usable products in an economically viable manner, among other reasons. Yet, significant progress has been made by employing lessons learned from the field of homogeneous and heterogeneous catalysis for the production of essential chemicals in the past. In this chapter, we will discuss the application of state-of-the-art heterogeneous and homogeneous catalyst technology with the potential to process lignocellulose to valuable platform molecules

A Catalytic Strategy for Selective Production of 5-Formylfuran-2-carboxylic Acid and Furan-2,5-dicarboxylic Acid

A novel catalytic strategy involving protective chemistry is presented for the selective production of 5-formylfuran-2-carboxylic acid (FFCA) and furan-2,5-dicarboxylic acid (FDCA) from concentrated 5-hydroxymethylfurfural (HMF) solutions. By protecting the reactive formyl group of HMF by acetalization with 1,3-propanediol (PDO), degradation and premature oxidation of HMF is suppressed. A hydroxyapatite-supported Au catalyst can selectively oxidize HMF-acetal in a 10 wt % solution to FFCA-acetal in 94 % yield in 2 hours at 373 K under 0.5 MPa of O 2. Deprotection of FFCA-acetal by mineral acids affords FFCA in 98 % yield and recovers nearly all PDO. FFCA in a 20 wt % solution can be oxidized to FDCA in 95 % yield under similar reaction conditions. The presented chemistry contributes to the development of novel manufacturing routes of prospective biobased monomer precursors using protecting agents

Oxidative Esterification of Acetal-Protected 5-Hydroxymethylfurfural to Dimethyl Furan-2,5-dicarboxylate with High Recovery of Protecting Agent

Polyalkylene furanoates are important prospective biobased substitutes for fossil-based terephthalates. Furanoate monomers can be obtained from the bioplatform 5-hydroxymethylfurfural (HMF), but practical applications are hindered due to its rapid oligomerization, which requires working in dilute solutions. Herein, we demonstrate a protection strategy based on acetalization of the reactive formyl group with propane-1,3-diol (PDO) to suppress oligomerization reactions. Following a stepwise approach, PDO-acetalized HMF (PD-HMF) was oxidatively esterified in a methanolic 20 wt % solution to mainly PDO-acetalized methyl-5-formylfuran-2-carboxylate (PD-MFFC) in a 91.0% yield in 6 h at 100 °C under 8 MPa air using a Au/CeO2 catalyst. The use of base could be decreased to 7.5 mol % Na2CO3 with respect to PD-HMF, which is a considerable advance over the state of the art. The loss of PDO due to oxidative degradation under these improved conditions was limited to 1.4%, implying that the protecting agent could be reused, which benefits the economic viability of the process. The PD-MFFC product stream, which contains a small amount of MeOH-acetalized MFFC, could be easily deprotected to obtain MFFC in a 99.1% yield with a PDO recovery degree of 93.1%. MFFC could readily be converted to dimethyl furan-2,5-dicarboxylate (MFDC) in a 96.6% yield via base-free oxidative esterification of MFFC in a methanolic 20 wt % solution in 2 h at 100 °C under 6 MPa air. The proposed stepwise approach combines high productivity (overall MFDC yield &gt;90%) and excellent PDO recovery (&gt;91%) using concentrated PD-HMF solutions (20 wt %).</p